This invention relates generally to antimicrobial peptides, and, more specifically, to .beta.-defensin peptides and their uses.
The cytoplasmic granules of polymorphonuclear leukocytes (neutrophils, PMN) contain numerous antimicrobial polypeptides which equip these cells to inactivate ingested microbial targets. These granule proteins constitute an antimicrobial arsenal which includes defensins, a family of broad spectrum antibiotic peptides which are released into the phagosome during phagolysosome fusion.
It has been previously demonstrated that the large granules of bovine neutrophils contain potent microbicidal peptides which are structurally distinct from defensins. These include three arginine-rich peptides, termed bactenecins, which efficiently kill several gram positive and gram negative bacteria in vitro. Recently, the isolation and characterization of a novel tridecapeptide amide from bovine neutrophils was reported. Termed indolicidin, this cationic peptide was shown to be unusually rich in tryptophan, and to have potent bactericidal activity against E. coli and S. aureus.
The ability to develop new therapeutics, especially against fungal and viral pathogens, is self evident. Discovery of new drugs of both classes is an urgent priority, as existing drugs are quite toxic and few in number.
In investigating the presence and biologic role of defensins in bovine neutrophils, a new antimicrobial peptide was discovered. Though possessing some features of defensins, namely their similar size, cationicity, and the presence of three intramolecular disulfides, the bovine peptides differ significantly in structure from defensins, and thus represent a new class of host defense peptides. To distinguish them from classical defensins, this novel peptide family is termed beta-defensins.